The present invention generally relates to an automated synthesis apparatus for compounds and a method of controlling the automated synthesis apparatus, and more particularly, to an automated synthesis apparatus for compounds and a method of controlling the automated synthesis apparatus capable of fully automatically synthesizing, with a computer controlled by programs, many derivatives of specific compound structure of various compounds.
In pharmaceutical research, one specific compound is required to be synthesized in large numbers respectively from various compounds so as to investigate the relationship between chemical structures and biological activity.
The conventional synthesizing operations are effected manually in accordance with experience. Most operations of quantifying the sample to supply it to a reaction vessel, of stirring the contents in the reaction vessel, of taking out reactant from the reaction vessel to move it to a purifying device, further washing the reaction vessel or the like after the completion of the manufacture of the products are manually effected mainly by researchers. Therefore, a lot of time and hands are required for this type of synthesizing operation which is necessary for pharmaceutical basic research.
Automation is demanded for this type of synthesizing operation. Conventionally, automated reaction apparatuses, of a batch type, or the like are provided to meet the demand. But automated apparatuses for purifying and isolating products followed by a series of synthesis procedure are hardly provided. In order to make the reactions optimum in the above described automated reaction apparatus, analyzing techniques using high performance liquid chromatography (HPLC) or the like, requiring the measurement for a comparatively long time period have to be used.
Therefore, the present invention provides an automated synthesis apparatus capable of automatically processing, as a series, the formation and isolation of compounds of a wide range from samples such as raw materials, regents, solvents or the like. The automated synthesis apparatus (such as disclosed in Japanese Laid-Open Patent Application Tokuheisho No. 2-2870) is composed of a synthesis processing apparatus I and a control apparatus II as shown in FIG. 21. The synthesis processing apparatus I is provided with a series of units composed of a sample supply unit 1, a reaction unit 2, a purifying unit 3, a hot & cold medium circulating unit 4, a washing solvent supply unit 5, an exhaust gas - drain water unit 6. Although not shown, a reaction tracing (reaction analysis) unit or the like may be additionally provided. Each unit of the above described synthesis processing apparatus I is connected, through an interface 9, with a computer 8 of the automated control apparatus II. Reference numeral 10 is a main power source.
Each of the above described units is controlled and operated in accordance with a program stored and inputted to the computer 8. In each service unit composed of the heating & cooling medium circulating unit 4, a washing solvent supplying unit 5 and the exhaust gas - drain water unit 6, the materials, reagents, catalysts, solvents and so on are fed to the reaction unit 2 from the sample supply unit 1 while the ambient conditions of the reaction unit 2 and the purifying unit 3 are being adjusted. The reaction processing such as heating, cooling, concentrating, PH adjusting and so on is effected in the reaction unit 2. A product produced through the reaction processing in the purifying unit 3 is purified so as to automatically obtain products.
A target compound to be produced by the above described automated synthesis apparatus varies over a wide range and the synthesizing procedures are different in accordance with the target compounds. Namely, a series of synthesizing procedure programs are different for each specific target compound, and an individual synthesizing procedure program is required in accordance of the specific target compounds.
Synthesizing procedure programs for automatically controlling the synthesis processing apparatus I as a series in accordance with the individual target compounds are very hard to make. For example, the sample supply unit 1 is provided with a plurality of volumetric tubes and liquid level boundary sensors for quantifying the raw materials, reagents, and solvents, and many flow lines for transferring to the next step the raw materials, the reagents, and solvents from each of the liquid storage containers and many electromagnetic valves for switching flow passages interposed in each flow line. The reaction unit 2 is provided with a plurality of reaction vessels for raw materials to be fed from the above described sample supply unit, a separator funnel where the reaction vessels and the tunnel contents (reaction mixture) can be circulated, a vessel for PH adjusting use where the reaction vessels and the reaction mixture can be circulated, and where the reagent can be fed from the above described sample supply unit 1.
Each unit has many components, and they are complicated in construction. The whole automated synthesis processing apparatus is provided with about one hundred fifty valves, about thirty relays, and about twenty sensors. Furthermore, flow lines which relate these elements organically are very complicated.
When creating a synthesizing procedure program for synthesizing one specific target compound, a sub-program (unit operation procedure) with the operating conditions of many electromagnetic valves, relays, and sensors arranged in order is required even for one operation procedure for feeding materials to the specific reaction vessel from, for example, a specific liquid storing container. The number of unit operation procedures necessary to reach a final stage for separately taking the target compound finally from a first stage of starting the material supply may be about one hundred.
Since the construction of an apparatus using hardware is extremely complicated, and the making of a software program for driving and controlling the hardware is complicated, the program maker has to be familiar with the knowledge of the hardware of the synthesis processing apparatus and its program. Otherwise, the program is impossible to make in reality. Even if the automation of the apparatus is made possible, it is very difficult to make programs for automatically controlling the apparatus in accordance with the target compound.
The above described problem is based on the fact that compounds to be synthesized by the automated synthesis apparatus cannot be formed using a single or a few synthesizing procedure programs, and different programs are respective.
The conventional program has a defect consisting of inferior flexibility in that it is incapable of stopping operation even when the reaction processing operation should be stopped in a case where, for example, the reaction is completed earlier than the reaction setting time, which is understood by viewing with the naked eye, with the operation control of the synthesis processing apparatus being effected as the program progresses.
In a conventional method of confirming the separation of two layers by the eyes of a person, the separation thereof in a separated liquid funnel and a PH adjusting cell and so on must be confirmed by a tester. Also, when the degree of skill of an experimenter is low, a confirmation error is likely to be caused, with a problem in that a separated liquid error and a PH adjustment error are likely to be caused by the operation error after the confirmation.
Therefore, an apparatus capable of automatically detecting the separation of two layers is desired, and also, two layers are desired to be automatically divided and be taken out by a separated liquid funnel, and the automatic adjustment of the PH is desired to be effected by the PH adjustment cell.